Anticancer Effects and Phytochemical Profile of Lavandula stoechas

<b>Background/Objectives:</b><i>Lavandula stoechas</i> has reported bioactivities, but its selective anticancer potential in human models remains insufficiently defined. This study aimed to compare cytotoxicity and selectivity of ethanol and methanol extracts prepared from fresh and dried <i>L. stoechas</i> and to profile candidate bioactive metabolites. <b>Methods:</b> Aerial parts <i>Lavandula stoechas</i> L. subsp. <i>stoechas</i> (<i>L. stoechas</i> L.) were extracted with ethanol or methanol from fresh (LsFE, LsFM) and dried (LsDE, LsDM) material. Cytotoxicity was assessed in cancer (MDA-MB-231, T98G, RT4) and non-malignant (hGF, ARPE-19) cells using Hoechst 33342-stained nuclear counts and MTS viability at 24-48 h. Metabolite identification was performed using LC-QTOF-MS in both positive and negative ESI modes, supported by database search results. <b>Results:</b> All extracts reduced viability in a dose- and time-dependent manner. Among them, the ethanol extract from fresh material (LsFE) displayed the highest cytotoxic potency and the most favorable selectivity profile, markedly reducing viability in breast (MDA-MB-231) and glioblastoma (T98G) cells while exerting only mild effects on non-malignant fibroblast (hGF) and retinal epithelial (ARPE-19) cells. In contrast, extracts from dried material, particularly LsDE, showed broader cytotoxicity across both cancerous and non-cancerous lines. LC-MS highlighted sesquiterpenoids (Kikkanol A; 3(4→5)-Abeo-4,11:4,12-diepoxy-3-eudesmanol), phenolics (tyrosol; 3,4-dihydroxybenzoic acid), flavonoid/ionone derivatives (luteolin 5,3'-dimethyl ether; 3-hydroxy-β-ionone), oxidized fatty acids (9(S)-HpODE, α-EpODE, 5,12-dihydroxy-eicosatetraenoic acid), and jasmonates (12-hydroxyjasmonic acid; dihydrojasmonic acid methyl ester), especially enriched in LsFE. <b>Conclusions:</b> Ethanol extracts of <i>L. stoechas</i> L., especially LsFE, demonstrated selective cytotoxicity against cancer cells while exerting relatively mild effects on non-malignant cells. The metabolite profile of <i>L. stoechas</i> L. extracts revealed a diverse composition, including phenolics, terpenoids, flavonoids, and oxidized lipids, which are commonly associated with biological activity. These results suggest that LsFE is a promising candidate for further studies focusing on compound isolation and mechanistic analysis.